ReviewFrontiers in psychiatry2026
The lactate-HCAR1 axis in exercise psychiatry: a candidate mechanism linking bone marrow-brain immunity to inflammation-related depression.
Review in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exercise is increasingly acknowledged as an effective intervention for depression, yet the biological mechanisms underlying its antidepressant effects remain incompletely defined. Conventional models have emphasized brain-centered pathways, including BDNF signaling, monoaminergic modulation, hypothalamic-pituitary-adrenal axis regulation, hippocampal neurogenesis, and synaptic plasticity. These mechanisms are important, but they may not fully explain depression phenotypes characterized by elevated inflammatory burden, fatigue, anhedonia, diminished motivation, psychomotor slowing, cognitive inefficiency, and altered peripheral immune activity. This review proposes that exercise-induced lactate should be considered not only as a metabolic substrate or byproduct, but also as a dynamic immunometabolic signal. Appropriately dosed exercise can generate a transient and recoverable lactate pulse that may be detected by immune, vascular, and brain-associated cells through hydroxycarboxylic acid receptor 1, also known as HCAR1 or GPR81. We propose that the lactate-HCAR1 axis could represent a candidate mechanism linking exercise metabolism to bone marrow myeloid regulation, peripheral inflammatory tone, brain vascular and border interfaces, glial responses, and inflammation-related depressive symptom dimensions. The framework integrates skeletal muscle metabolism, myelopoiesis, peripheral myeloid cells, blood-brain interfaces, microglia, astrocytes, and endothelial cells into a cross-organ model of exercise psychiatry. Importantly, the strength of evidence differs across this pathway: some components are supported by human exercise physiology or preclinical causal studies, whereas others remain inferential and require validation in patients with depression. We therefore frame lactate-informed exercise prescription as a testable translational hypothesis rather than a clinically established strategy. Future studies should examine lactate kinetics, inflammatory biomarkers, immune cell phenotypes, symptom dimensions, safety, recovery dynamics, and comparisons with conventional heart-rate-, VO
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.